Fatty liver disease determines the progression of coronary artery calcification in a metabolically healthy obese population

Abstract

Objectives: Metabolically healthy obese (MHO) phenotype describes an obese state with a favorable metabolic profile. However, the prognosis of this subpopulation remains controversial. We aimed to examine whether MHO phenotype is associated with progression of atherosclerotic activity, reflected as the changes in coronary artery calcification (CAC) over time. If so, we sought to determine the role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this progression.

Methods: We enrolled 1,240 asymptomatic subjects who underwent repeated CAC score measurement during routine health examinations. CAC score progression was defined as either incident CAC in a population free of CAC at baseline, or an increase by ≥2.5 units between the baseline and final square root of CAC scores in participants with detectable CAC at baseline. Subjects were stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography.

Results: Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score progression. The MHO phenotype was not significantly associated with CAC score progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval [CI], 0.93-2.25), as compared to the metabolically healthy non-obese (MHNO) phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was significantly associated with CAC score progression (multivariate adjusted-OR, 2.37; 95% CI, 1.34-4.16), as compared to the MHNO/no FLD phenotype, whereas the MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71-2.24).

Conclusions: Obese individuals with FLD have an increased risk of atherosclerosis progression, despite their healthy metabolic profile. Preventive interventions targeting cardiometabolic risk factors should be considered in such individuals, regardless of the weight status.

Fig 1. Percentage of coronary artery calcification progressors in the 4 categories of metabolic health and obesity.

Fig 2. Illustration of the odds ratios (ORs) and 95% confidence intervals (CI) for the progression of coronary artery calcification according to metabolic health, obesity, and the presence of fatty liver disease.

The ORs were adjusted for age, sex, waist circumference, drinking, smoking, exercise habits, baseline CAC score, LDL-C, hsCRP, and follow-up interval.